Methods of treating premalignant and malignant growths of the skin have often been traumatic. A common method of treating disorders such as actinic keratosis has been the application of liquid nitrogen to destroy the affected tissue. Epidermal tumors are commonly treated by physical removal through surgery. A method which has been used in the past is chemosurgery through the application of escharotic or fixative chemicals such as zinc chloride. This has not been found to be particularly effective because of the physical discomfort associated with the use of such materials. It also has the disadvantage of destroying both healthy tissue and the diseased tissue.
The use of known antitumor drugs has not been found to be particularly effective in the treatment of skin tumors since these drugs are commonly applied systemically resulting in substantial side effects due to their toxicity. The naturally occurring meso form of the catecholic butane, nordihydroguaiaretic acid [meso-1,4-bis (3,4-dihydroxyphenyl)-2,3-dimethylbutane] ("NDGA") was reported as providing a positive result against malignant melanoma, C. R. Smart, et al., Rocky Mountain Medical Journal, Nov. 1970, pp. 39-43 (unless otherwise indicated, NDGA is used herein to refer to the meso form of nordihydroguaiaretic acid). NDGA is found in the creosote bush, and this plant was used for centuries to brew a tea which was the basis for a folk remedy that called for drinking the tea to cure colds, rheumatism and other ailments. However, this remedy has not proven to be successful.
A clinical study was conducted by Smart, et al. in which human cancer patients ingested either a tea made from the creosote bush or doses of pure NDGA. This study indicated that neither NDGA nor the tea were effective anticancer agents and in some cases caused stimulation of tumor cell growth. This confirmed the earlier screening studies of NDGA conducted by Leiter et al. of the Cancer Chemotherapy National Service Center of the National Cancer Institute which obtained negative results when NDGA was tested against several types of cancer cells.
The general structure for nordihydroguaiaretic acid (generic to all of its stereoisomeric forms) is given in Formula (I). ##STR1##
Surprisingly, it has been discovered that the catecholic butane, nordihydroguaiaretic acid, and/or derivatives thereof as defined herein, in a pharmaceutical composition that includes ionic zinc, is effective in treating benign, premalignant and malignant growths of the skin without the detrimental side effects associated with chemotherapy or chemosurgical techniques. The compositions provide their advantageous results when applied topically to the afflicted area of the skin, or injected into the growth. As disclosed in copending application Ser. No. 699,923, such compositions are also effective in treating disorders of the skin including acne and psoriasis, in aiding in the healing of skin wounds and in alleviating bacterial, viral and fungal infections when applied to the situs of the disorder. The compositions are also useful in the treatment for warts.